MicroRNA In Human Saliva May Help Diagnose Oral Cancer

Researchers continue to add to the diagnostic alphabet of saliva by identifying the presence of at least 50 microRNAs that could aid in the detection of oral cancer, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"It is a Holy Grail of cancer detection to be able to measure the presence of a cancer without a biopsy, so it is very appealing to think that we could detect a cancer-specific marker in a patient's saliva," said Jennifer Grandis, M.D., professor of otolaryngology and pharmacology at the University of Pittsburgh School of Medicine and Cancer Institute and a senior editor of Clinical Cancer Research.

MicroRNAs are molecules produced in cells that have the ability to simultaneously control activity and assess the behavior of multiple genes. They are a thriving research topic right now, and researchers believe they could hold the key to early detection of cancer. The emergence of a microRNA profile in saliva represents a major step forward in the early detection of oral cancer.

"The oral cavity is a mirror to systemic health, and many diseases that develop in other parts of the body have an oral manifestation," said David T. Wong, D.M.D., D.M.Sc., Felix and Mildred Yip Endowed Professor at the University of California, Los Angeles School of Dentistry.

Wong and colleagues measured microRNA levels in the saliva of 50 patients with oral squamous cell carcinoma and 50 healthy control patients. They detected approximately 50 microRNAs.

Two specific microRNAs, miR-125a and miR-200a, were present at significantly lower levels in patients with oral cancer than in the healthier controls.

Wong said that the findings of this study would have to be confirmed by a larger and longer analysis.

Source: ScienceDaily (Aug. 26, 2009)

Delivering Medicine Directly into a Tumor

Peptide Delivers Anti-Cancer Compounds to Where They Can Do the Most Good

Researchers at Burnham Institute for Medical Research at University of California, Santa Barbara have identified a peptide (a chain of amino acids) that specifically recognizes and penetrates cancerous tumors but not normal tissues. The peptide was also shown to deliver diagnostic particles and medicines into the tumor. This new peptide, called iRGD, could dramatically enhance both cancer detection and treatment. The work is being published December 8 in the journal Cancer Cell.

Led by Erkki Ruoslahti, M.D., Ph.D., distinguished Burnham professor at UCSB, this research was built on Dr. Ruoslahti’s previous discovery of “vascular zip codes,” which showed that blood vessels in different tissues (including diseased tissues) have different signatures. These signatures can be detected and used to dock drugs onto vessels inside the diseased tissue. In addition to homing in on tumor vessels, the new iRGD peptide penetrates them to bind inside the tumor. Previous peptides have been shown to recognize and bind to tumors, but were unable to go beyond the tumor blood vessels. 

“This peptide has extraordinary tumor-penetrating properties, and I hope that it will make possible substantial improvements in cancer treatment,” says Dr. Ruoslahti. “In our animal studies, the iRGD peptide has increased the efficacy of a number of anti-cancer drugs without increasing their side effects. If these animal experiments translate into human cancers, we would be able to treat cancer more effectively than before, while greatly reducing the side effects the patient would suffer.” 

The novel iRGD peptide, identified by using phage display for a peptide that binds to the blood vessels of pancreatic and bone tumors, was tested to determine its ability to penetrate tumors. Researchers injected fluorescent-labeled iRGD into tumor-bearing mice and found that the peptide accumulated in a variety of tumors, including prostate, breast, pancreatic, brain and other types. In addition, the peptide only targeted the tumors and did not accumulate in normal tissue.

Iron oxide nanoworms, which can be visualized by magnetic resonance imaging, were coupled to the peptide and shown to penetrate the tumors, whereas uncoupled nanoworms could not. This demonstrates that iRGD can deliver diagnostics to tumors. The anti-cancer drug Abraxane was also shown to target, penetrate and spread more within tumor tissue when coupled to iRGD than with other formulations.